What is the recommended starting dose of atomoxetine for ADHD and the optimal time of day to administer it?

Atomoxetine Starting Dose and Optimal Timing

Start atomoxetine at 40 mg orally once daily in the morning for adults and children over 70 kg, or 0.5 mg/kg/day for children and adolescents up to 70 kg, and administer it as a single morning dose for optimal adherence and tolerability. 1, 2

Starting Dose Guidelines

Weight-Based Dosing

• For patients ≤70 kg: Initiate at 0.5 mg/kg per day (approximately 40 mg daily) 1
• For patients >70 kg (including adults): Start with 40 mg orally once daily 1, 2
• This conservative starting dose minimizes early adverse effects while establishing tolerability 1

Titration Schedule

• Maintain the initial 40 mg dose for at least 7-14 days before any dose increase to assess tolerability 1, 2
• After the initial period, increase to 60 mg daily, then if needed to 80 mg daily 1, 2
• Dose escalations should occur no more frequently than every 7-14 days to avoid behavioral activation, agitation, or other adverse effects 1
• The target therapeutic dose is 1.2 mg/kg/day (approximately 80 mg for most adults), which has demonstrated optimal efficacy 3

Maximum Dose Limits

• The maximum recommended dose is the lesser of 1.4 mg/kg/day or 100 mg/day 1, 2
• Doses exceeding this threshold do not improve efficacy and increase adverse-effect risk 1
• The 1.8 mg/kg/day dose provides no additional benefit over 1.2 mg/kg/day 3

Optimal Timing of Administration

Once-Daily Morning Dosing (Preferred)

• Administer atomoxetine as a single dose in the early morning 1, 2
• Once-daily morning dosing has been proven effective in controlled trials and improves medication adherence 3
• This timing minimizes potential sleep disturbances, as insomnia can occur with atomoxetine 2

Alternative Divided Dosing

• Atomoxetine can alternatively be given as divided doses in early morning and late afternoon/early evening if tolerability issues arise with once-daily dosing 3
• However, single morning dosing is generally preferred for simplicity and compliance 3

Critical Titration Principles

Slow Titration Rationale

• Gradual dose increases (smallest available increments at 1-2 week intervals) are better tolerated and help avoid exceeding the optimal dose 1
• Rapid dose escalation increases risk of behavioral activation/agitation, including motor restlessness, insomnia, impulsiveness, talkativeness, disinhibited behavior, and aggression 1
• Younger patients are more susceptible to behavioral activation with rapid dose increases 1

Response Timeline

• Atomoxetine requires 6-12 weeks to achieve full therapeutic effect, unlike stimulants which work within hours 1
• Setting appropriate patient expectations about this delayed response is essential to prevent premature discontinuation 1

Safety Monitoring Requirements

Mandatory Monitoring Parameters

• Monitor closely for suicidal ideation, clinical worsening, and unusual behavioral changes, especially during the first few months of treatment or after dose adjustments 1, 2
• Obtain baseline and monitor blood pressure, heart rate, height, and weight at follow-up visits 1

Common Adverse Effects

• Nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence are the most common side effects 1, 2
• These effects are generally mild to moderate and transient 4
• If side effects occur, consider returning to the previous well-tolerated dose 1

Clinical Pitfalls to Avoid

• Do not increase doses more frequently than every 7-14 days, as this significantly increases risk of behavioral activation 1
• Do not exceed 100 mg/day or 1.4 mg/kg/day, as higher doses provide no additional benefit and increase adverse effects 1
• Do not expect immediate symptom improvement—counsel patients that full effect takes 6-12 weeks 1
• Do not use atomoxetine as first-line therapy—it is recommended as second-line when stimulants fail or are not tolerated 1